The characterization of idiotypic determinants and the generation of anti-idiotypic reagents have provided powerful tools with which to analyze a given immune response. The idiotype network developed during the course of an immune response provides conceptual insight into the host response to a given antigen. It is proposed to assess the vaccine potential of various monoclonal anti-idiotypic antibody (anti-Id) reagents which result from potential idiotype networks initiated by a host in response to hepatitis B virus (HBV) infection or immunization with hepatitis B surface antigen (HBsAg). Monoclonal anti-Id reagents will be generated against human antibodies to HBsAg (anti-HBs). These anti-Id will be serologically characterized in order to assess whether they are representative of Ab-2 beta internal image or Ab-2 alpha subclasses of anti-Id. The ability of these different classes of anti-Id to modulate the immune response to HbsAg in experimental animals will be examined. The anti-Id induced anti- HBs (Ab-3) responses will be analyzed for idiotype expression. Possible genetic restriction reported in other systems with the Ab-2 alpha classes of anti-Id will be examined in the anti-HBs system using different inbred strains of mice for anti-Id immunization. The potential effects the different classes of monoclonal anti-Id may have on the serological characteristics of an anti-HBs (Ab-3) response will be determined and compared relative to immunization with the nominal antigen (HBsAg). In addition, we will compare the vaccine potential of the various monoclonal anti-Id to that of recombinant HBsAg purified from baculovirus in small experimental animals. Finally, we will examine the idiotype heterogeneity of the human immune response to HBsAg utilizing those monoclonal anti-Id which detect shared anti-HBs idiotypes present in HBV infected and HBsAg vaccinated individuals. The results of this study will provide insight into the vaccine potential of monoclonal anti-Id for preventing HBV infection. Additionally, these studies should provide information concerning whether idiotype networks, expression of particular idiotype, or both are important in the host response to HBV.